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Transcriptional Regulation of the Urokinase Receptor (u-PAR) – A Central Molecule of
Invasion and Metastasis

Abstract

The phenomenon of tumor-associated proteolysis
has been acknowledged as a decisive step in the
progression of cancer. This short review focuses on
the urokinase receptor (u-PAR), a central molecule
involved in tumorassociated invasion and metastasis,
and summarizes the transcriptional regulation of
u-PAR. The urokinase receptor (u-PAR) is a heavily
glycosylated cell surface protein and binds the serine
protease urokinase specifically and with high affinity.
It consists of three similar cysteinerich repeats and
is anchored to the cell membrane via a GPI-anchor.
The u-PAR gene comprises 7 exons and is located on
chromosome 19q13. Transcriptional activation of the
u-PAR promoter region can be induced by binding of
transcription factors (Sp1, AP-1, AP-2, NF-κB). One
current study gives an example for transcriptional
downregulation of u-PAR through a PEA3/ets transcriptional
silencing element. Knowledge of the molecular
regulation of this molecule in tumor cells
could be very important for diagnosis and therapy in
the near future.

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